摘要
Abstract
Background and Aims:Breast cancer is the most prevalent malignancy among women worldwide,and chemotherapy resistance and tumor recurrence remain major obstacles to long-term survival.Dysregulation of apoptosis is considered a key mechanism underlying chemoresistance;however,the synergistic roles of apoptosis-and chemotherapy-related genes in prognostic stratification and drug resistance have not been fully elucidated.This study aimed to construct a multigene prognostic risk model based on apoptosis-and chemotherapy-related genes and to further investigate the role of the key gene in breast cancer stemness and chemoresistance.
Methods:Transcriptomic and clinical data of breast cancer patients were obtained from The Cancer Genome Atlas(TCGA).Differentially expressed apoptosis-and chemotherapy-related genes were identified,and a multigene prognostic risk model was constructed using univariate Cox regression,LASSO regression,and multivariate Cox regression analyses.The predictive performance of the model was evaluated by time-dependent ROC curves,nomograms,and an external GEO dataset.Associations between the risk score and clinical characteristics,immune cell infiltration,and chemotherapeutic drug sensitivity were further analyzed.Functional assays,including wound healing,Transwell invasion,and Western blot analyses,were performed to validate the biological role of the key gene in breast cancer cells.
Results:A prognostic signature comprising 10 apoptosis-and chemotherapy-related genes was established.The model demonstrated favorable predictive performance in the TCGA cohort,with AUC values of 0.705 and 0.650 for 3-and 5-year overall survival rate,respectively,and was further validated in an external GEO dataset(3-year AUC=0.741).The risk score was identified as an independent prognostic factor and was significantly associated with advanced TNM stage,increased infiltration of immunosuppressive cells,and resistance to chemotherapeutic agents,including NU7441 and fludarabine.PCDHB2 was highly expressed in high-risk patients,and its knockdown markedly inhibited migration and invasion of MDA-MB-231 cells while reducing the expression of the stemness-related protein SOX2.
Conclusion:This study established a robust multigene prognostic model based on apoptosis-and chemotherapy-related genes for risk stratification and personalized survival prediction in breast cancer.PCDHB2 may contribute to chemoresistance by regulating cancer stemness,highlighting its potential as a novel therapeutic target and providing new insights into breast cancer precision therapy.关键词
乳腺肿瘤/多基因风险模型/免疫微环境/肿瘤干性/预后Key words
Breast Neoplasms/Multigene Risk Model/Immune Microenvironment/Cancer Stemness/Prognosis分类
医药卫生
